A BIOMARKER THAT IDENTIFIES SENESCENT HUMAN-CELLS IN CULTURE AND IN AGING SKIN IN-VIVO
A BIOMARKER THAT IDENTIFIES SENESCENT HUMAN-CELLS IN CULTURE AND IN AGING SKIN IN-VIVO
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DOI：
10.1073/pnas.92.20.9363
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发表时间：
1995-09-26
影响因子：
11.1
通讯作者：
CAMPISI, J
中科院分区：
文献类型：
--
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
正常的体细胞在有限的分裂次数后，总是进入不可逆转的生长停滞和功能改变的状态。这一过程被称为复制性衰老，被认为是一种肿瘤抑制机制，也是衰老的潜在原因。有充分的证据表明，避免衰老或永生对于恶性转化是重要的。相比之下，复制衰老在生物体衰老中的作用是有争议的。对来自不同年龄、遗传背景或物种的捐赠者培养的细胞的研究表明，衰老发生在体内，组织寿命和细胞复制寿命受到共同的基因控制。然而，衰老细胞不能与组织中静止或终末分化的细胞区分开来。因此，缺乏衰老细胞在体内存在并随年龄积累的证据。我们发现几个人类细胞在培养衰老时表达一种β-半乳糖苷酶，这种酶在pH值为6时可被组织化学检测到。该标记在衰老的成纤维细胞和角质形成细胞中表达，但在静止的成纤维细胞和终末分化的角质形成细胞中不表达。在永生细胞中也没有这种基因，但它是由逆转永生的遗传操作诱导的。在来自不同年龄的人类捐赠者的皮肤样本中，真皮成纤维细胞和表皮角质形成细胞中这一标记的表达随年龄的增加而增加。这一标记提供了体内衰老细胞可能存在并随年龄积累的原位证据。
Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.